β Cells Can Be Generated from Endogenous Progenitors in Injured Adult Mouse Pancreas

Novel strategies in diabetes therapy would obviously benefit from the use of beta (β) cell stem/progenitor cells. However, whether or not adult β cell progenitors exist is one of the most controversial issues in todayʹs diabetes research. Guided by the expression of Neurogenin 3 (Ngn3), the earliest islet cell-specific transcription factor in embryonic development, we show that β cell progenitors can be activated in injured adult mouse pancreas and are located in the ductal lining. Differentiation of the adult progenitors is Ngn3 dependent and gives rise to all islet cell types, including glucose responsive β cells that subsequently proliferate, both in situ and when cultured in embryonic pancreas explants. Multipotent progenitor cells thus exist in the pancreas of adult mice and can be activated cell autonomously to increase the functional β cell mass by differentiation and proliferation rather than by self-duplication of pre-existing β cells only.